Is BMP6 p.Arg396= (c.1188G>T) pathogenic?

BMP6 p.Arg396= (c.1188G>T) is classified Likely benign in BMP6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-22). Rare (popmax 0.433%, mid); Associated with BMP6-related disorder.

What condition is associated with BMP6 p.Arg396= (c.1188G>T)?

BMP6 p.Arg396= (c.1188G>T) is associated with BMP6-related disorder (ClinVar).

How common is BMP6 p.Arg396= (c.1188G>T) in the general population?

BMP6 p.Arg396= (c.1188G>T) is rare (popmax 0.433%, mid) (gnomAD).

BMP6 p.Arg396=

c.1188G>T · rs201606023 · VCV3056476

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.433%, mid)

Conditions

BMP6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.2, phastCons 1
Overall
CADD	5.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.433% Middle Eastern · 26/6,004 alleles

Filtering AF 0.303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.26%

Overall 0.0134% 216/1,614,002 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.433%	231
South Asian	0.128%	778
Remaining individualsnot grpmax-eligible	0.0144%	6,943
European (non-Finnish)	0.00542%	18,437

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BMP6
Protein: p.Arg396=
Coding: c.1188G>T
MANE Select: NM_001718
dbSNP: rs201606023
Type: single nucleotide variant
Location: chr6:7862482 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 69.74 · 5 PDB
Residue 396: a UniProt-annotated variant site (in io; associated with disease susceptibility); the 'disordered' region

Full BMP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BMP6-related disorder

Similar variants

BMP6 c.1392+7T>G Likely benign same condition
BMP6 c.665-3T>C Likely benign same condition
BMP6 p.Ala189= Likely benign same condition
BMP6 p.Ala189Thr Benign same condition
BMP6 p.Ala212= Benign same condition
BMP6 p.Ala343= Benign same condition
BMP6 p.Arg28Gln Benign same condition
BMP6 p.Asp354= Benign same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bmp6-p-arg396 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown